# Analysis of factors controlling coxsackievirus population dynamics in the intestine

> **NIH NIH F32** · WASHINGTON UNIVERSITY · 2020 · $61,909

## Abstract

Project Summary
The gastrointestinal (GI) tract is a dynamic ecosystem, regulating nutrient absorption, infection,
commensalism, and immunity in vibrant homeostasis. The GI tract includes physical, chemical, molecular, and
immune barrier to infection. Despite these barriers, enteroviruses, including coxsackievirus B3 (CVB3),
successfully transit the GI barrier to initiate infection, spread throughout the host causing disease in diverse
tissues, and finally be shed in stool. The essential molecular and anatomic features of the GI tract that restrict
or render hosts susceptible to enterovirus infection are only beginning to be understood. Additionally, host
barriers dramatically affect pathogen population dynamics. This is fundamentally important because intrahost
enterovirus population dynamics directly affect pathogenesis. However, the effect of the GI tract on CVB3
population dynamics is completely unexplored. The long-term objectives for this project is to define the
intestinal molecular and cellular pressures that effect CVB3 evolution and pathogenesis. The immediate goals
of this project are to: 1) precisely map the kinetics, tissues, and cells involved in CVB3 replication in the GI
tract; 2) assess CVB3 population dynamics, including founding population size, in the intestine; 3) test the role
of host factors, including interferon and sex, on intestinal CVB3 replication and population dynamics. These will
be accomplished in the following specific aims: Specific Aim 1: Categorize the cell types CVB3 infects in the
intestine of male and female mice by A) identifying specific infected cell types by cell sorting, B) determining
infection site and kinetics using reporter viruses, C) assessing the role of immune cells on intestinal infection
by depleting specific cells. Specific Aim 2: Examine CVB3 population dynamics and routes of dissemination in
male and female mice by A) developing and validating a library of isogenic barcoded CVB3 strains, B) creating
a spatio-temporal atlas of CVB3 population dynamics by sequencing viruses from tissues and specific cell
types, and C) depleting immune cells and assessing spread and transmission of CVB3. The knowledge
gained in this work will be a critical step to understanding the role of the GI tract in modulating CVB3 genetics,
evolution, and pathogenesis.

## Key facts

- **NIH application ID:** 10065277
- **Project number:** 7F32AI138392-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Broc Taylor McCune
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $61,909
- **Award type:** 7
- **Project period:** 2020-01-01 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10065277

## Citation

> US National Institutes of Health, RePORTER application 10065277, Analysis of factors controlling coxsackievirus population dynamics in the intestine (7F32AI138392-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10065277. Licensed CC0.

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